1. Field of the Invention
This invention is directed to methods for embolizing blood vessels which methods are particularly suited for treating vascular lesions. In these methods, a non-particulate agent such as a metal coil is introduced into a vascular site (e.g., an aneurysm cavity) in conjunction with an embolizing composition comprising a biocompatible polymer and a biocompatible solvent.
The biocompatible solvent is miscible or soluble in blood and also solubilizes the polymer during delivery. The biocompatible polymer is selected to be soluble in the biocompatible solvent but insoluble in blood. Upon contact with the blood, the biocompatible solvent dissipates from the embolic composition whereupon the biocompatible polymer precipitates. Precipitation of the polymer in the presence of the non-particulate agent permits the agent to act as a structural lattice for the growing polymer precipitate.
2. References
The following publications are cited in this application as superscript numbers:
1 Castaneda-Zuniga, et al., Interventional Radiology, in Vascular Embolotherapy, Part 1, 1:9-32, Williams & Wilkins, Publishers (1992) PA0 2 Hopkins, et al., "Endovascular Treatment of Aneurysms and Cerebral Vasospasms", in "Current Management of Cerebral Aneurysms", Am. Assoc. Neuro. Surgeons, A. Awad, Editor, Chapter II, pp. 219-242 (1993). PA0 3 Pruvo, et al., "Endovascular Treatment of 16 Intracranial Aneurysms with Microcoils", Neuroradiology, 33 (suppl):S144 (Abstract) (1991). PA0 4 Mandai, et al., "Direct Thrombosis of Aneurysms with Cellulose Acetate Polymer", J. Neurosurg., 77:497-500 (1992) PA0 5 Kinugasa, et al., "Direct Thrombosis of Aneurysms with Cellulose Acetate Polymer", J. Neurosurg., 77:501-507 (1992) PA0 6 Casarett and Doull's Toxicology, Amdur et al., Editors, Pergamon Press, New York, pp. 661-664 (1975) PA0 7 Greff, et al., U.S. Pat. application Ser. No. 5,667,767 for "Novel Compositions for Use in Embolizing Blood Vessels", issued Sep. 16, 1997 PA0 8 Greff, et al., U.S. Pat. application Ser. No. 5,580,568 for "Cellulose Diacetate Compositions for Use in Embolizing Blood Vessels", issued Dec. 3, 1996 PA0 9 Kinugasa, et al., "Early Treatment of Subarachnoid Hemorrhage After Preventing Rerupture of an Aneurysm", J. Neurosurg., 83:34-41 (1995) PA0 10 Kinugasa, et al., "Prophylactic Thrombosis to Prevent New Bleeding and to Delay Aneurysm Surgery", Neurosurg., 36:661 (1995) PA0 11 Taki, et al., "Selection and Combination of Various Endovascular Techniques in the Treatment of Giant Aneurysms", J. Neurosurg., 77:37-42 (1992) PA0 12 German, et al., New England Journal of Medicine, 250:104-106 (1954) PA0 13 Rabinowitz, et al., U.S. Pat. No. 3,527,224, for "Method of Surgically Bonding Tissue Together", issued Sep. 8, 1970 PA0 14 Hawkins, et al., U.S. Pat. No. 3,591,676, for "Surgical Adhesive Compositions", issued Jul. 6, 1971
All of the above references are herein incorporated by reference in their entirety to the same extent as if each individual reference was specifically and individually indicated to be incorporated herein by reference in its entirety.
3. State of the Art
Embolization of blood vessels is conducted for a variety of purposes including the treatment of tumors, the treatment of lesions such as aneurysms, arteriovenous malformations (AVM), arteriovenous fistula (AVF), uncontrolled bleeding and the like.
Embolization of blood vessels is preferably accomplished via catheter techniques which permit the selective placement of the catheter at the vascular site to be embolized. In this regard, recent advancements in catheter technology as well as in angiography now permit neuro endovascular intervention including the treatment of otherwise inoperable lesions. Specifically, development of microcatheters and guide wires capable of providing access to vessels as small as 1 mm in diameter allows for the endovascular treatment of many lesions.
Endovascular treatment regimens include the use of non-particulate agents such as metal coils which are designed to induce thrombosis after delivery to the vascular site..sup.1 Ideally, after placement of the microcoils at the vascular site, thrombosis results in the formation of a clot about the coil thereby sealing the vascular site.
Complications in this procedure have, however, been reported including the fact that thrombosis about the metal coil is not uniform in nature and fragmentation of the resulting clot can occur. This former aspect can lead to incomplete sealing of, for example, vascular lesions, whereas the latter aspect can lead to migration of the blood clots in the patient's circulation.
Additionally, while platinum has been the metal of choice for use in metal coils, the thrombogenic potential of platinum coils is variable.sup.2 and can result in incomplete sealing of the blood vessel (e.g., aneurysm). Likewise, when employed in treating aneurysms, coils are prone to migration in and/or from the aneurysm cavity after placement.sup.2. Coil migration away from the aneurysm cavity in such cases has been reported to result in regressive complete motor paralysis in treated patients..sup.3 Likewise, migration within the aneurysm cavity prior to thrombosis can liberate calcified emboli from within the aneurysm cavity and cause intimal tears and vessel wall dissections..sup.2
Still further, in the embolization of blood vessels, the choice of coil size is critical because the use of microcoils which are too small can result in coil migration within the patient's circulation and the use of coils which are too large for the blood vessel to be embolized can result in coil elongation which is recognized to be less efficient for blood vessel embolization..sup.1
While efforts have been made to improve the thrombogenic properties of platinum coils by the incorporation of Dacron.RTM. threads onto the coils, coil migration remains a serious concern primarily due to potential severe adverse affects arising from such migration. Moreover, since thrombosis around the coils is essential for successful treatment of the aneurysm, care must be taken to minimize any breakage of clot fragments from the formed clot and incorporation of these fragments into the patient's circulation.
Still further, in treatment of lesions, it is common to employ multiple coils to effect thrombosis. However, the positioning and placement of multiple coils is technically challenging and often results in undesired coil migration, misplacement and/or altered shape of the coil pack.
In view of the above there is an ongoing need to enhance the efficacy of blood vessel embolization using non-particulate agents such as metal coils.
This invention is directed to the discovery that the efficacy of blood vessel embolization via catheter delivery of microcoils and other non-particulate agents to the blood vessel site to be embolized can be enhanced by further delivering a polymer composition as described below to this site. The deposited coils or other non-particulate agents act as a lattice about which a polymer precipitate grows thereby embolizing the blood vessel.
While the use of polymer compositions to embolize blood vessels has heretofore been disclosed including compositions wherein a preformed polymer precipitates in situ from a carrier solution at the vascular site to be embolized,.sup.4,5 such compositions invariably have been employed by themselves in the absence of non-particulate agents such as metal coils. For effective treatment, such polymer compositions must form a precipitate in the blood vessel having sufficient structural integrity to inhibit fragmentation of the precipitate and the precipitate must be anchored at the site of placement. While certain polymer compositions form precipitates having the requisite structural integrity.sup.7,8, other polymer compositions do not. In either case, anchoring of these precipitates to the vascular site remains a serious problem particularly in lesions having high blood flow and/or diffuse necks. In such cases, precipitate anchoring to the vascular site is not an intrinsic function of the shape of the lesion to be treated and migration of the precipitate away from the intended vascular site can occur.
In view of the above, there is an ongoing need for enhancing the efficacy of polymer compositions used for embolizing vascular sites.